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Professor and Chair, Department of Obstetrics, Gynecology and Reproductive Sciences

The University of Texas Medical School at Houston, Houston, TX, USA

Robert Resnik MD

Professor Emeritus of Reproductive Medicine

UCSD School of Medicine

Solana Beach, CA, USA

Jean Rex MD

Instructor, Department of Pediatrics

Washington University School of Medicine

St. Louis, MO, USA

Adam A. Rosenberg MD

Professor of Pediatrics, University of Colorado Denver School of Medicine

and The Children’s Hospital

Aurora, CO, USA

Dwight J. Rouse MD

Attending Physician, Maternal-Fetal Medicine Division

Women & Infants Hospital of Rhode Island

Professor of Obstetrics and Gynecology

Warren Alpert School of Medicine at Brown University

Providence, RI, USA

George Saade MD

Professor, Department of Obstetrics and Gynecology

Chief of Obstetrics and Maternal-Fetal Medicine

Director, Perinatal Research Division

The University of Texas Medical Branch

Galveston, TX, USA

Michael Schatz MD, MS

Chief, Department of Allergy

Kaiser-Permanente Medical Center

San Diego, CA, USA

James R. Scott MD

Professor and Chair Emeritus

Department of Obstetrics and Gynecology

University of Utah Medical Center

Salt Lake City, UT, USA

Jeanne S. Sheffield MD

Director, Maternal-Fetal Medicine Fellowship

University of Texas Southwestern Medical Center

Dallas, TX, USA

Baha M. Sibai MD

Professor and Director of Clinical Perinatal Research

University of Cincinnati College of Medicine

Cincinnati, OH, USA

Robert M. Silver MD

Professor of Obstetrics & Gynecology

Chair of Maternal-Fetal Medicine

University of Utah Health Sciences Center

Salt Lake City, UT, USA

Lynn L. Simpson MD

Associate Professor of Obstetrics and Gynecology

Columbia University Medical Center

New York, NY, USA

Sindhu K. Srinivas MD

Department of Obstetrics & Gynecology

Washington University School of Medicine

St Louis, MO, USA

Jorge E. Tolosa MD MSCE

Associate Professor of Obstetrics and Gynecology

Oregon Health and Science University

Portland, OR, USA

Carl P. Weiner MD, MBA

K.E. Krantz Professor & Chair, Obstetrics and Gynecology

Professor, Molecular & Integrative Physiology

University of Kansas School of Medicine

Kansas City, KS, USA

George D. Wendel MD

Professor, Department of Obstetrics & Gynecology

University of Texas Southwestern Medical Center

Dallas TX, USA

Katharine D. Wenstrom MD

Professor, Obstetrics & Gynecology

Director, Divison of Maternal-Fetal Medicine

Women & Infants’ Hospital of Rhode Island

Brown Alpert Medical School

Providence, RI, USA

Erika Werner MD

Instructor, Yale University School of Medicine

Department of Obstetrics, Gynecology and Reproductive Sciences

New Haven, CT, USA

Marsha Wheeler MD

Department of Obstetrics & Gynecology

University of Colorado Health Sciences Center

Denver, CO, USA

Deborah A. Wing MD

Professor and Director, Division of Maternal-Fetal Medicine

Department of Obstetrics and Gynecology

University of California, Irvine, CA, USA

Jerome Yankowitz MD

University of Iowa Hospitals and Clinics

Department of Obstetrics and Gynecology

Division of Maternal-Fetal Medicine and Fetal Diagnosis and Treatment Unit

Iowa City, IA, USA

Preface

Today’s pressures of managed care, rapidly changing technology, and medically sophisticated patients who always expect good outcomes, make it essential to have correct information at hand. The nature and training of physicians instills the constant drive to do the right thing. Therefore, it is necessary to have appropriate, current, and practical information available as protocols to make good decisions. Why use protocols? Having a protocol or guideline organizes essential clinical material in a systematic, logical order and avoids omissions in patient care. It is to that end that we have created Protocols for High-Risk Pregnancies

Evaluating all pregnancies for risk factors is an effective way of identifying patients who need additional care. Some patients have factors present from the outset of pregnancy such as diabetes or history of prematurity that place them at increased risk. Others start with a normal pregnancy but subsequently develop risk factors such as pre-eclampsia or premature rupture of the membranes. This may develop quickly and therefore, it is important to have a protocol for management. Of course, care must be taken to be sure that the term “high risk” does not cause alarm or anxiety for your patient.

Since the 4th edition was published, advances in medical knowledge and technology have dictated changes in management. Thus, in this 5th edition all original protocols have been updated. New ones have been added to cover such advances as nuances in Doppler and sonography, as well as changes in the approach to prematurity, diabetes, hypertension, prophylactic immunizations, among others. We have also included protocols in areas of critical importance to the developing world, such as malaria, tuberculosis, and chronic anemia. For each protocol we have invited the physicians whom we believe to be the outstanding authorities on the topics. They start with a brief introduction and pathophysiology and write the protocols as if they were working up their patient and following her through the various stages of management. We require that each protocol is evidence-based to the extent that is possible. In areas where no evidence exists we have asked the experts to make recommendations. There is some intentional overlap in protocols, as medicine is an art as well as a science. All protocols represent the individual thoughts and opinions of these experts.

We realize that the future will bring new medical advances and that new editions of Protocols will need to be published in a timely fashion, thus we welcome your comments for future incorporation. We thank Martin Sugden, Lewis O’Sullivan, and the excellent editorial and production staff at Wiley-Blackwell for their professional skills.

This edition, as with the others, was created to be practical, cost effective and clearly presented: a format that is easy to carry with you on rounds and consultations. We have designed this book to help you in your practice. Make it you own!

Exposures to potentially hazardous agents during pregnancy are common. Such agents include drugs (both therapeutic agents and abused substances), environmental chemicals, infectious agents, physical agents (radiation, heat and mechanical factors) and maternal health conditions. Many of these exposures are not readily avoidable, as pregnancy is often not planned or recognized for an extended period after conception, or because there is a continuing need for maternal treatment for health conditions (e.g. epilepsy, infection, asthma, chronic cardiovascular disorders). Exposure to various agents in the home or workplace, or as a consequence of maternal lifestyles and self-medication, is almost universal, and pre-conception planning only rarely provides an opportunity to identify exposures of concern. As a consequence, questions about the significance of such an exposure, whether stated or not, are often a source of concern to pregnant women or their care provider.

Not all developmental toxicants need result in permanent adverse outcomes for the fetus or newborn. Some agents may have at least partially reversible or transient effects if recognized early, such as fetal growth restriction from tobacco smoking. It is important to recognize that structural birth defects resulting from exposure to human teratogens are not the only manifestations of exposure to developmental toxicants. Fetal or postnatal growth disorders, functional developmental disorders including cognitive and behavioral deficits, abnormalities of placental function putting the fetus at increased risk, and death (embryonic, fetal, perinatal or postnatal) are all among potential manifestations of exposures. Furthermore, some adverse outcomes may not become apparent until many years later (e.g. reproductive consequences and cancer from exposure to diethylstilbestrol).

Pathogenetic factors in evaluation of risk from exposure to teratogens and other developmental toxicants

When evaluating the likely significance of exposure to potentially hazardous agents, it is essential to consider the following issues in the context of the known or likely pathogenetic mechanisms for adverse fetal outcomes.

Dose and duration of exposure

In general, the larger the dose, the more likely an effect, and the more likely the effect will be significant.

Likewise, the longer the duration of exposure, the greater the chance that susceptible periods of organogenesis and development will be encountered.

Timing

Timing of exposure is critical: certain organ systems may have a limited period of susceptibility for damage.

Although it is commonly thought that damage can only result during the period of organogenesis, i.e. during the first trimester, this is not correct. Some organ systems (e.g. the brain) undergo developmental processes later in pregnancy and can be damaged throughout the prenatal period.

Pathogenetic mechanism(s)

Teratogens and developmental toxicants produce their adverse effect by specific mechanisms. As these mechanisms are often important in multiple tissues and organs, it is not surprising that several specific types of damage may result.

Those agents that affect basic morphogenetic processes commonly are related to first trimester exposures. However, those agents which act through mechanical pressures are likely to have the greatest impact during the third trimester, and those agents that produce necrosis through inflammation and/or hemorrhage can potentially destroy normally developing structures throughout pregnancy.

Host susceptibility

Variability in the genetic factors related to metabolism of drugs and chemicals may result in differential susceptibility of the host. These pharmacogenetic factors must be expressed at a relevant time in the tissue or organ system affected.

There are two potentially relevant ‘hosts’ to be considered. Mother and embro/fetus only share 50% of the genome. Thus, depending on the pathogenesis of the adverse outcome, maternal or fetal (or perhaps both) genotype may be more important.

Exposures to human teratogens and developmental toxicants commonly are manifest across a wide spectrum of effects. At the severe end, a clinically recognizable pattern of effects (a ‘syndrome’) may be identified. However, variability of manifestations within the scope of specific adverse outcomes comprising a syndrome is the rule. Among the population of exposed and affected infants, less severe and less pervasive manifestations are often more frequent. Thus infants exposed to alcohol prenatally may have outcomes ranging from mild effects on cognition and behavior from smaller amounts consumed on a few occasions, to the full-blown fetal alcohol syndrome.

presents a list of agents, including therapeutic agents, for which substantial human data is available establishing a risk for humans.

The list continues to grow as new research reveals more details about the magnitude and nature of risks associated with many of these and other newly recognized agents. Thus it is important to check the current literature before counseling an exposed family. A variety of information resources, ranging from Internet-based computerized databases and commercially available information resources, to standard reference resources for further reading are listed in .

Information resources: computerized databases

Database

Contact

REPROTOX

(202) 687-5137

TERIS

(206) 543-2465

For the clinician whose practice only rarely encounters these questions, or for those who encounter a question for which current data is limited or difficult to access, consultation with a specialist may be an appropriate option. Many states or academic centers have established Teratogen Information Services to help meet this need. presents a current listing of these resources.

Teratogen information services in North America

For information regarding the Teratology Information Service in your area, contact the Organization of Teratology Information Services (OTIS) at: (866) 626-6847 or .